Individuals who develop diseases in association with antibodies or T lymphocytes which react with self structures are said to have autoimmunity. Autoimmune disorders, most of which are connective tissue diseases, probably result from environmental agents acting upon genetically-susceptible hosts with subsequent immune activation and pathology. We are studying the epidemiology and pathogenesis of human autoimmune diseases to define etiologic factors, devise more effective therapies, and ultimately possibly prevent some of these diseases. Specific projects include: A) A study of human leukocyte antigen (HLA), T cell receptor (TCR), and immunoglobulin (Gm) genes associated with autoantibodies specific to a group of diseases, which are characterized by chronic inflammation of muscle or myositis. Within the last year, the laboratory has used molecular HLA DR, DP, and DQ gene typing of genomic DNA, collected from over 250 myositis patients representing all the major clinical and autoantibody groups, to show associations of DR-beta, DQ-alpha, and Gm allotype genes with each of the myositis-specific autoantibodies and with certain clinical subgroups. Similar molecular studies of TCR gene expression in the periphery and target organs of myositis patients are also underway. Preliminary results suggest that TCR restrictions exist in target tissues. B) Worldwide studies of the epidemiology of myositis attempting to associate immunogenetics, clinical signs and symptoms, geographic location, season of disease-onset, and therapeutic responses in the different clinical and autoantibody subsets. Preliminary data suggests that strong associations of the above do exist, and that seasonal and geographic clustering of myositis onset occurs in groups of patients defined by myositis-specific autoantibodies. C) Foods, drugs, biologics, devices and other environmental agents, that have been implicated in the development of connective tissue diseases, are being investigated re specific host risk factors associated with these disorders, and the clinical, serologic and genetic differences from that seen in the same idiopathic diseases.